The localization of acyl coenzyme A-carnitine acyltransferases in rat liver cells.
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Biomedical subjects
Publications and source records attributed to K R Norum.
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Children with cystic fibrosis (CF) often have a poor vitamin A status. We found in the present work a reduced level of serum retinol in older children with this disease. As retinol enters intestinal lymph as retinyl esters, the enzyme acyl-CoA:retinol acyltransferase (ARAT) may be of importance for retinol absorption. We have assayed ARAT activity in duodenal mucosal homogenate from children with CF. There was a large variation within the group. However, mean ARAT activity was not significantly decreased, as compared with controls. Thus, the lack of pancreatic enzymes probably is the main reason for reduced vitamin A absorption in CF. In celiac disease and in lactose intolerance--both mucosal disorders--a significant reduction of mean ARAT activity was found.
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We have studied the effect of retinoids, forskolin and TNF-alpha on two sublines of U937 cells, U937/clone 4 and U937/GTB. Retinoids induced differentiation of U937/clone 4, while the U937/GTB cells were resistant to induction of differentiation by retinoids. Retinoids effectively reduced the proliferation of both U937/clone 4 and U937/GTB, and decreased the steady state levels of c-myc mRNA in both sublines. Furthermore, the retinoid resistant U937/GTB cells were hypersensitive to the cytotoxic effect of TNF-alpha. Forskolin increased the cAMP level in the U937/clone 4 cells 14 times above basal level, but did not change the cAMP concentration in the U937/GTB cells.
Some 50 years ago, Müller described hypercholesterolemia, xanthomas, and coronary heart disease as symptoms of a genetic disorder. In the 1930s, other important discoveries concerning inborn errors of metabolism were made in Norway. Følling described phenylketonuria, and Refsum examined his first patients with heredopathia atactica polyneuritiformis (phytanic acid storage disease). Several other inborn errors of metabolism have been discovered in Norway: familial lecithin-cholesterol acyltransferase deficiency, methylmalonic acidemia, beta-methylcrotonyl-coenzyme A carboxylase deficiency, pyroglutamic aciduria, and N-acetyl aspartic aciduria. Metabolic and biochemical studies in these patients have revealed new and important metabolic pathways. Studies on patients with inborn errors not first described in Norway have also given important information on key enzymes in metabolic pathways. Thus, studies on patients with cerebrotendinous xanthomatosis and those with Zellweger's syndrome have revealed the normal metabolic route for conversion of cholesterol to bile acids. The discoveries and the clinical and biochemical research in former days were mostly good examples of serendipity combined with excellent clinical alertness. In more recent years, several of the discoveries have resulted from systematic biochemical screening of urine, plasma, or other body fluids from patients with unusual clinical syndromes.
The effect of various antiepileptics on the retinol storage in rat liver was tested. We observed a dose- and time-dependent reduction in the hepatic storage of retinol after the administration of several of these drugs. Administration for 11 weeks of phenobarbital, primidone and carbamazepine in doses comparable to those used in humans reduced the retinol concentration in the Liver by 17-33% compared to control rats. The plasma retinol levels remained unaffected in all the rats. Plasma retinol from 31 epileptic children had plasma levels between 0.7 and 2.4 nmol/ml, which is regarded as normal.
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